Diabetes mellitus (Type I) affects over 100 million individuals world-wide and approximately 1.5 million in the U.S., this disease results in direct medical and indirect non-medical costs (e.g., disability, premature mortality) of as much as 10 billion dollars annually. Clinical trials of human islet transplantation have demonstrated the feasibility of reversing diabetes. However, two major problems (immunorejection and an insufficient quantity of islets) have limited its use as a standard treatment. Primary xenograft tissue (e.g., quantity of islets) have limited its use as a standard treatment. Primary xenograft tissue (e.g., from pigs) offers the potential to overcome the shortage of transplantable tissue, but presents additional risks, such as the transmission of zoonotic disease. Another approach would involve the in vitro expansion of islets in vulture. We have recently shown that would involve the in vitro expansion of islets in culture. We have recently shown that co-culture of islets with a novel biomaterial derived from the small intestine submucosa (SIS): (1) increase islet mass, (2) increases islet insulin response to glucose, (3) increases the islet insulin content, and (4) induces proliferating cell nuclear-antigen on islet cells. Collectively, these data suggest that one or more components in SIS cause islet, specifically beta, cell proliferation in vitro. The goal of this proposal is to identify this proliferative components for use in an effective in vitro expansion system for pancreatic islets. PROPOSED COMMERCIAL APPLICATION: Typed 1 diabetes affects approximately 1.5 million people in the U.S. resulting in a cost of approximately 10 billion dollars annually. Development of a product that will promote the proliferation of pancreatic islets in vitro would enhance the use of islet transplantation as a cure for the disease.